Amikacin Sulfate

Antibacterial; aminoglycoside derived from kanamycin.1 2 3 4

Administration

Administer by IV infusion or IM injection.1 2 3

Has been given intrathecally† or intraventricularly† as an adjunct to IV or IM administration for treatment of meningitis and other CNS infections.4 19 33 34 35 37 38 39

Patients should be well hydrated to minimize chemical irritation of renal tubules which may occur as the result of high urine amikacin concentrations.1 2 3

Renal function should be assessed prior to and daily during therapy.1 2 3

For solution and drug compatibility information, see Compatibility under Stability.

IV Infusion

If a β-lactam (e.g., cephalosporin, penicillin) is administered concomitantly, the drugs should not be admixed and should be administered separately.1 2 3 HID

Dilution

IV solutions are prepared by adding 500 mg to 100–200 mL of 0.9% sodium chloride, 5% dextrose, or other compatible IV solution (see Solution Compatibility under Stability).1 2 3

For pediatric patients, the volume of infusion fluid depends on the patient's needs, but should be sufficient to allow an infusion period of 1–2 hours in infants or 30–60 minutes in older children.1 2 3

Rate of Administration

In adults, administer appropriate dose by IV infusion over 30–60 minutes.1 2 3

In infants, administer appropriate dose by IV infusion over 1–2 hours;1 2 3 in older children, administer by IV infusion over 30–60 minutes.1 2 3

IM Injection

Appropriate dose of commercially available injection containing amikacin in a concentration of 50 or 250 mg/mL should be given undiluted.1 2 3 IM injections have been given into the upper outer quadrant of the buttocks.16

Dosage

Available as amikacin sulfate; dosage expressed in terms of amikacin.1 2 3

IV and IM dosage is identical.1 2 3

Dosage should be individualized taking into consideration patient’s pretreatment body weight, renal status, severity of infection, and susceptibility of the causative organisms.1 2 3 4 11 200 201 202 203 204 216

Many clinicians recommend that dosage be determined using appropriate pharmacokinetic methods for calculating dosage requirements and patient-specific pharmacokinetic parameters (e.g., elimination rate constant, volume of distribution) derived from serum concentration-time data.11 200 201 202 203 204 216

Whenever possible, especially in patients with life-threatening infections, suspected toxicity or nonresponse to treatment, decreased or varying renal function, and/or when increased aminoglycoside clearance (e.g., patients with cystic fibrosis, burns) or prolonged therapy is likely, peak and trough serum concentrations of amikacin should be determined periodically and dosage should be adjusted to maintain desired serum concentrations.4 11 207 216 219 222 223 228 236 237

When conventional dosage regimens (i.e., multiple daily doses) are used, many clinicians recommend that dosage be adjusted to maintain peak and trough serum concentrations of 15–30 and <5–10 mcg/mL, respectively.4 11 14 216 222 225 226 227 238 239 Amikacin serum concentrations >30–35 mcg/mL may be associated with toxicity.14 The manufacturers state that peak serum concentrations (obtained 30–90 minutes after administration) of >35 mcg/mL and trough serum concentrations (obtained just before the next dose) of >10 mcg/mL should be avoided.1 2 3

Once-daily administration† of aminoglycosides is at least as effective as, and may be less toxic than, conventional dosage regimens employing multiple daily doses.11 48 49 50 52 56 62 74 75 76 205 206 207 208 209 210 211 212 213 214 215 216 217 228 229 230 231 232 233 234 235 243 245 246 247 248

Usual duration of treatment is 7–10 days.1 2 3 Safety of aminoglycoside treatment for >14 days not established.1 2 3 If clinical response does not occur within 3–5 days, in vitro susceptibility should be reassessed.1 2 3 In difficult and complicated infections, use of amikacin should be re-evaluated if treatment >10 days is being considered.1 2 3 If the drug is continued, serum amikacin concentrations and renal, auditory, and vestibular functions should be monitored closely.1 2 3

Pediatric Patients

General Dosage for Neonates IV or IM

Manufacturer recommends an initial loading dose of 10 mg/kg followed by 7.5 mg/kg every 12 hours.1 2 3

Neonates <1 week of age: AAP recommends 7.5 mg/kg every 18–24 hours for those weighing <1.2 kg, 7.5 mg/kg every 12 hours for those weighing 1.2–2 kg, and 7.5–10 mg/kg every 12 hours in those weighing >2 kg.6

Neonates 1–4 weeks of age: AAP recommends 7.5 mg/kg every 18–24 hours for those weighing <1.2 kg, 7.5–10 mg/kg every 8 or 12 hours for those weighing 1.2–2 kg, and 10 mg/kg every 8 hours for those weighing >2 kg.6

AAP states the drug is inappropriate for treatment of mild to moderate infections.6

Once-daily† regimen: Full-term neonates have received 15 mg/kg once daily.48 56 76

General Dosage for Infants and Children IV or IM

Older infants and children: Manufacturers recommend 15 mg/kg daily given in 2 or 3 equally divided doses (i.e., 7.5 mg/kg every 12 hours or 5 mg/kg every 8 hours).1 2 3

Children ≥1 month of age: AAP recommends 15–22 mg/kg given in 3 divided doses for severe infections.6

AAP states the drug is inappropriate for treatment of mild to moderate infections.6

Once-daily† regimen: Children have received 15–20 mg/kg once daily.50 54 62 74 76

Mycobacterial Infections† Active Tuberculosis† IV or IM

Children <15 years of age: 15–30 mg/kg (up to 1 g) once daily or twice weekly.6 218

Children ≥15 years of age: 15 mg/kg daily (up to 1 g) as a single daily dose (usually 750–1000 mg daily) 5–7 times weekly for the first 2–4 months or until culture conversion; dosage can then be reduced to 15 mg/kg daily (up to 1 g) given 2 or 3 times weekly, depending on efficacy of the other drugs in the regimen.218

Must be used in conjunction with other antituberculosis agents.218 Multiple-drug regimen usually given for 12–18 months when rifampin-resistant M. tuberculosis are involved; for 18–24 months when isoniazid- and rifampin-resistant strains are involved; or for 24 months when the strain is resistant to isoniazid, rifampin, ethambutol, and/or pyrazinamide.218

Meningitis IV or IM

15–20 mg/kg daily given in 2 divided doses for neonates ≤7 days of age and 20–30 mg/kg daily given in 3 divided doses in older neonates and children.64 77 Smaller doses and longer intervals between doses may be indicated in neonates weighing <2 kg.64 77

Empiric Therapy in Febrile Neutropenic Patients† IV

Children 1–17 years of age: 20 mg/kg once daily or 6.5 mg/kg 3 times daily has been given in conjunction with IV ceftazidime.62

Adults

General Adult Dosage IV or IM

15 mg/kg daily given in 2 or 3 equally divided doses (i.e., 5 mg/kg every 8 hours or 7.5 mg/kg every 12 hours).1 2 3

Once-daily† regimen: 15 mg/kg once daily has been used.11 49

Meningitis and Other CNS Infections IV

15 mg/kg daily given in 3 divided doses.77

Intrathecal† or Intraventricular†

4–20 mg as a single daily dose in conjunction with IM or IV administration of the drug (7.5 mg/kg every 12 hours).4 19 33 35 37

Urinary Tract Infections (UTIs) Uncomplicated Infections IV or IM

250 mg twice daily.1 2 3

Mycobacterial Infections† Active Tuberculosis† IV or IM

15 mg/kg daily (up to 1 g) as a single daily dose (usually 750–1000 mg daily) 5–7 times weekly for the first 2–4 months or until culture conversion; dosage can then be reduced to 15 mg/kg daily (up to 1 g) given 2 or 3 times weekly, depending on efficacy of the other drugs in the regimen.218

Adults >59 years of age: 10 mg/kg (up to 750 mg) daily.218

Must be used in conjunction with other antituberculosis agents.218 Multiple-drug regimen usually given for 12–18 months when rifampin-resistant M. tuberculosis are involved; for 18–24 months when isoniazid- and rifampin-resistant strains are involved; or for 24 months when the strain is resistant to isoniazid, rifampin, ethambutol, and/or pyrazinamide.218

Other Mycobacterial Infections† IV or IM

Mycobacterium avium complex† (MAC) infections: 7.5–15 mg/kg daily in conjunction with other antimycobacterial anti-infectives.58 59 60 61

IV

M. abscessus† or M. fortuitum† infections: 10–15 mg/kg daily in 2 divided doses in conjunction with other antimycobacterial anti-infectives.9

Nocardia Infections† IV or IM

5–7.5 mg/kg every 12 hours.69

Empiric Therapy in Febrile Neutropenic Patients† IV

7.5 mg/kg twice daily has been given in conjunction with IV ceftazidime or IV cefepime.63

Prescribing Limits

Pediatric Patients

IV or IM

Daily dosage should not exceed 15 mg/kg or 1.5 g.1 2 3

Adults

IV or IM

Daily dosage should not exceed 15 mg/kg or 1.5 g.1 2 3

Special Populations

Renal Impairment

Dosage adjustments necessary in patients with renal impairment.4 6 11 14 24

One method suggested by manufacturer is an initial loading dose of 7.5 mg/kg followed by 7.5 mg/kg given at intervals (in hours) calculated by multiplying the patient's steady-state serum creatinine (in mg/dL) by 9.1 2 3 The dosing method of Sarubbi and Hull, which is based on corrected creatinine clearance, also has been recommended.h

The above dosage calculation methods should not be used in patients undergoing hemodialysis or peritoneal dialysis.h In adults with renal failure undergoing hemodialysis, some clinicians recommend supplemental doses of 50–75% of the initial loading dose at the end of each dialysis period.14 Others suggest supplemental doses may not be necessary in patients undergoing short-term hemodialysis.51 Serum concentrations of the drug should be monitored in dialysis patients and dosage adjusted to maintain desired serum concentrations.14 51

Active Tuberculosis† IV or IM

ATS, CDC, and IDSA recommend that usual doses be given at less frequent intervals since use of lower doses may reduce efficacy of the drug.218 These experts recommend 12–15 mg/kg 2 or 3 times weekly.218 In addition, if the patient is receiving hemodialysis, the dose should be given after the procedure is finished and serum concentrations of the drug should be monitored to avoid toxicity.218

Geriatric Patients

Select dosage with caution and closely monitor renal function because of age-related decreases in renal function.1 2 3 4

No dosage adjustments except those related to renal impairment.1 2 3 (See Renal Impairment under Dosage and Administration.)

• Advise patients that antibacterials (including amikacin) should only be used to treat bacterial infections and not used to treat viral infections (e.g., the common cold).1 2

• Importance of completing full course of therapy, even if feeling better after a few days.1 2

• Advise patients that skipping doses or not completing the full course of therapy may decrease effectiveness and increase the likelihood that bacteria will develop resistance and will not be treatable with amikacin or other antibacterials in the future.1 2

• Importance of maintaining adequate fluid intake.1 2 3

• Importance of informing clinician if there is evidence of ototoxicity (dizziness, vertigo, tinnitus, roaring in the ears, hearing loss), other neurotoxicity (numbness, skin tingling, muscle twitching, seizures), or nephrotoxicity (e.g., decreased urine output).1 2 3

• Importance of informing clinician of existing or contemplated therapy, including prescription and OTC drugs.1 2 3

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1 2 3

• Importance of advising patients of other important precautionary information.1 2 3 (See Cautions.)